Analysis of lung carcinogenesis by hnRNP B1, a RNA binding protein, using SPC-hnRNP B1 transgenic mouse models

使用 SPC-hnRNP B1 转基因小鼠模型分析 RNA 结合蛋白 hnRNP B1 的肺癌发生

• 批准号: 14570555
• 负责人: SUEOKA Eizaburo
• 金额: $ 2.24万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570555/
• 关键词: Lung Cancer; RNA biniding protein; hnRNP B1; transgenic mouse; surfactant Protein C; 肺癌

We identified that hnRNP B1, a splicing variant of hnRNP A2, was overexpressed in nuclei of human lung cancer cells, from the early stage to the advanced : Moreover, hnRNP B 1 was overexpressed in squamous cell carcinoma in various organs, such as oral cavity and esophagus, in addition to lung. To clarify the role of hnRNP B1 for lung carcinogenesis, we constructed the chimeric genes fused with surfactant protein C promoter and hnRNP B1 cDNA. We obtained several transgenic clones of SPC-hnRNP BI, hnRNP A2 and GFP after introduction into ES cell neclei. Heterogenic transgenic mice were back-crossed to parental wild mice and we obtained F3 generations and homogygous mouse clones. High expression levels of hnRNP B1 protein were confirmed in the lungs of homogygous mice by immunohistocherriistry. Recent our study found hnRNP B1 interacted with a DNA repair protein complex and regulated its activity. To determine the precise role of hnRNP B1 in lung carcinogenesis associated with alteration of DNA repair activity, sequential analysis of pathological and cytogenetical analyses were under investigation.

我们发现hnRNP B1是hnRNP A2的剪接变体，在早期至晚期的人肺癌细胞的细胞核中过表达。此外，hnRNP B 1在除肺外的各种器官的鳞状细胞癌中过表达，如口腔和食管。为了阐明hnRNPB 1在肺癌发生中的作用，我们构建了融合表面活性蛋白C启动子和hnRNPB 1 cDNA的嵌合基因。将SPC-hnRNP B1、hnRNP A2和GFP基因导入ES细胞后，获得了多个转基因克隆。将异源转基因小鼠与亲本野生小鼠回交，获得F3代和同型小鼠克隆。hnRNP B1蛋白在同卵小鼠肺组织中有高水平表达。最近我们的研究发现hnRNP B1与DNA修复蛋白复合物相互作用并调节其活性。为了确定hnRNP B1在肺癌发生中与DNA修复活性改变相关的确切作用，正在研究病理学和细胞遗传学分析的顺序分析。

项目成果

Iwanaga K, Sueoka N, Akemi S, Sakuragi T: "Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer"Cancer Letters. 202. 71-79 (2003)

Iwanaga K、Sueoka N、Akemi S、Sakuragi T：“tob（一种新型肿瘤抑制基因产物）的表达或磷酸化状态的改变是肺癌的早期事件”Cancer Letters。

Tominaga M, Sueoka N, Irie K, Iwanaga K, Tokunaga O, Hayashi S, Nakachi K, Sueoka E.: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin Dl, and Ki

Tominaga M、Sueoka N、Irie K、Iwanaga K、Tokunaga O、Hayashi S、Nakachi K、Sueoka E.：“使用 hnRNP B1 结合细胞周期相关标记物 p16 检测和区分肺腺癌的癌前和早期阶段，

Iwanaga K: "Alteration of expression or phosphorylation status of tob, a novel tumor suppress or gene product, is an early event in lung cancer."Cancer Letter. 202. 71-79 (2003)

Iwanaga K：“tob 的表达或磷酸化状态的改变是一种新型肿瘤抑制或基因产物，是肺癌的早期事件。”《癌症信》。

Fujimoto N, Sueoka N, Sueoka E, Okabe S, et al.: "Lung cacner prevention with (-)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoprotein B1."Int.J.Oncol.. 20. 1233-1239 (2002)

Fujimoto N、Sueoka N、Sueoka E、Okabe S 等人：“通过异质核核糖核蛋白 B1 进行监测，用 (-)-表没食子儿茶素没食子酸酯预防肺癌。”Int.J.Oncol.. 20. 1233-1239 (2002)

Wu S, Sato M, Endo C, Sakurada A, Dong B, Aikawa H, Chen Y, Okada Y, Matsumura, Y.Sueoka E, Kondo T.: "hnRNP B1 pirotein may be a possible prognostic factor in squamous cell carcinoma of the lung."Lung Cancer. 41. 179-186 (2003)

Wu S、Sato M、Endo C、Sakurada A、Dong B、Aikawa H、Chen Y、Okada Y、Matsumura、Y.Sueoka E、Kondo T.：“hnRNP B1 pirotein 可能是鳞状细胞癌的一个可能的预后因素